The mesolimbic dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) has been implicated in the neurobiological actions of many drugs of abuse. However, the complexity of this system presents a significant barrier to investigation of its function. Thus, scientists have studied its components in fragments. In the proposed work, fast-scan cyclic voltammetry will be used to measure subsecond changes in dopamine concentration in the NAc with dual channel extracellular electrophysiology recordings of neuronal activity taken simultaneously in both the NAc and VTA. The electrochemical data will be analyzed with principal component regression, allowing dopamine concentration changes to be objectively distinguished from other electrochemical contributors and selectively quantitated. This combined approach will allow for the determination of the precise relationship between rapid dopamine release and the electrical activity at both ends of this pathway. The size of the probe in the NAc will be optimized to provide information on the geometry of the synaptic ensembles being sampled. Once characterized the methodology will be used to investigate the effects of cocaine on this reward-related brain circuitry.